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This is a multi-center, single-blind, randomized, active-controlled, clinical trial in Percutaneous Coronary Intervention [PCI] subjects. Subjects will be randomized to receive the Combo stent as the investigational treatment arm or an EES as the active-control arm.

Up to 50 sites are proposed in Japan and the United States to enroll 286 subjects (271 evaluable) in each of 2 arms, for a total sample size of 572 subjects (542 evaluable) who are admitted to the hospital for a planned (elective and urgent) percutaneous coronary artery intervention procedure.

After stent implantation, subjects will be contacted for follow-up at 30 days; 6 months; and 1, 2, 3, 4, and 5 years. At 12 months a clinical evaluation will be completed before cardiac catheterization and angiographic assessment.

Collaboration between with Japan and the United States as a "Proof of Concept" program under the auspices of the Harmonization by Doing Initiative, WG 1, including concomitant enrollment in U.S.A. sites as an FDA-approved IDE study

The Combo Stent is composed of the OrbusNeich R stent™, with an abluminal coating of a bioabsorbable polymer matrix formulated with sirolimus for sustained release, and an anti-CD34 antibody cell capture coating on the luminal surface.

Device: OrbusNeich Combo stent™

The Combo Stent is composed of the OrbusNeich R stent™, with an abluminal coating of a bioabsorbable polymer matrix formulated with sirolimus for sustained release, and an anti-CD34 antibody cell capture coating on the luminal surface.

The primary clinical endpoint of TVF, defined as cardiac death, target-vessel MI, or ischemia-driven TVR by percutaneous or surgical methods, at 1 year. Primary endpoints will be reported after all subjects have completed 12 months of follow-up. A total of 572 subjects are enrolled to ensure that 542 subjects are evaluable for the primary clinical endpoint, across all cohorts.

The secondary efficacy endpoint is mechanistic OCT healthy level of intimal tissue coverage, determined by the OCT core laboratory at 1 year for subjects in Cohorts A and B combined (total N=140 subjects).

Additional prespecified endpoints include clinically and functionally ischemia-driven TLR, including use of target-vessel FFR, analyzed dichotomously using the Fractional Flow Reserve (FFR) vs. Angiography in Multivessel Evaluation (FAME) study criteria of 0.8 during a 2 minute infusion of adenosine or adenosine triphosphate.34 Abnormal FFR-driven interventions at 1 year will be included in the evaluation of ischemia-driven TLR.

Serum will be assessed for HAMA development at index, 30 days, and 12 months in Cohort B subjects. Human antimurine antibody plasma assessment will be with blood draws performed during index procedure, 30 day follow-up visit, and 1 year catheterizations.

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Ages Eligible for Study:

20 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria

To be eligible for this trial, subjects must meet all of the following criteria:

Subject is able to verbally confirm understanding of risks, benefits, and treatment alternatives of Combo vs EES stent, and the subject or a legally authorized representative (LAR) must provide written informed consent before any study-related procedures are performed.

Subject must be at least 20 years of age at the time of randomization.

Subject must have clinical or functional evidence of myocardial ischemia (eg, stable or unstable angina, stabilized non-ST-elevation MI confirmed by serum markers, ischemia by positive functional study, abnormal FFR, or a reversible change in the electrocardiogram [ECG] consistent with ischemia).

Subject must be acceptable candidate with anatomy suitable for PCI with a DES.

Subject agrees to return for all study-related follow-up assessments, including invasive OCT follow-up assessment at 6 months (Cohort A) and at 1 year postprocedure (Cohorts A, B, and C).

Subject is an acceptable candidate for CABG surgery.

Angiographic Anatomy Criteria—

Target lesions must be located in a native coronary artery with visually estimated diameter of 2.5 mm to 3.5 mm, inclusive, and up to 3 de novo target lesions may be treated, with a maximum of 2 de novo target lesions per epicardial vessel, with a maximum of 2 target vessels.

Target lesions should be treatable with a single stent, and must measure 28 mm or less in length by visual estimation (2 mm or more of nondiseased tissue on either side of the target lesion should be covered by the study stent).

If more than 1 target lesion will be treated, the reference vessel diameter and lesion length of each target lesion must meet the above criteria.

Target lesions must be in a major artery or branch with a visually estimated stenosis of 50% or greater and less than 100% with a TIMI flow of 1 or greater.

Previous percutaneous intervention of lesions in a target vessel (including side branches) is allowed if done 9 or more months before the study procedure and greater than 10 mm from the current target lesion.

Nonstudy percutaneous interventions for lesions in a nontarget vessel are allowed if done 9 or more months before the study procedure, in the absence of documented ischemia or angiographic restenosis related to the vessel.

Exclusion Criteria

If a subject meets any of the following criteria, he or she may not be enrolled in the study:

Subject has known hypersensitivity or contraindication to aspirin; both heparin and bivalirudin; all available P2Y12 inhibitors (clopidogrel, prasugrel, ticlopidine, and ticagrelor); any everolimus, sirolimus, cobalt, chromium, nickel, tungsten, acrylic, or fluoro polymers; or hypersensitivity to contrast media that cannot be adequately premedicated.

Subject has previously received murine therapeutic antibodies and exhibited sensitization through the production of HAMAs.

Subject has elective surgery planned within the first 12 months after the procedure that will require interruption or discontinuation of planned DAPT.

Subject has known platelet count less than 100,000 cells/mm3 or greater than 700,000 cells/mm3, a white blood cell count of less than 3000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis).

Subject has known renal insufficiency (eg, serum creatinine level of greater than 2.5 mg/dL or subject is on dialysis).

Subject has history of bleeding diathesis or coagulopathy or will refuse blood transfusions.

Subject has had a cerebrovascular accident or transient ischemic neurological attack within the past 6 months.

Subject has had a significant gastrointestinal or urinary bleed within the past 6 months.

Known other medical illness (eg, cancer, chronic infectious disease, severe vascular disease, or congestive heart failure) or known history of substance abuse (alcohol, cocaine, heroin, etc.) that may cause noncompliance with the protocol, confound the data interpretation, or is associated with a life expectancy of less than 1 year.

Currently participating in another clinical study that has not yet reached its primary endpoint.

Currently pregnant or breast-feeding or is planning pregnancy in the period up to 1 year following index procedure. Female subjects of childbearing potential must have a negative pregnancy test within 7 days before the index procedure.

Angiographic Exclusion Criteria—

If the target lesion meets any of the following criteria, the subject may not be enrolled in the study:

Unprotected left main coronary artery location.

Unprotected ostial (located within 2 mm of the origin) left anterior descending artery or left circumflex.

Located within an arterial or saphenous vein graft or graft anastomosis, distal to a diseased arterial or saphenous vein graft (visually estimated graft diameter stenosis greater than 40%).

Involves a bifurcation in which the side branch is 2 mm or greater in diameter AND would be covered by the planned stent.

Involves a side branch requiring predilation.

Total occlusion (TIMI flow 0) before wire crossing.

Extreme tortuosity proximal to or within the lesion.

Extreme angulation (90º or greater) proximal to or within the lesion.

Heavy calcification, defined as multiple persisting opacifications of the coronary wall visible in more than one projection surrounding the complete lumen of the coronary artery at the site of the lesion.

Restenotic vessel from previous intervention.

Received brachytherapy in any epicardial vessel (including side branches).

Target vessel contains angiographically visible thrombus.

Serial lesions or diffuse disease with high probability of bailout requiring 3 or more stents in a single vessel, more than 5 stents per subject, or more than 2 vessels.

Target or nontarget vessel lesion (including all side branches) is present with a high probability of requiring PCI within 12 months after the index procedure.